Three-Dimensional Patient-Derived In Vitro Sarcoma Models: Promising Tools for Improving Clinical Tumor Management
Over the past decade, the development of new targeted therapeutics directed against specific molecular pathways involved in tumor cell proliferation and survival has allowed an essential improvement in carcinoma treatment. Unfortunately, the scenario is different for sarcomas, a group of malignant n...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-09-01
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| Series: | Frontiers in Oncology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fonc.2017.00203/full |
| _version_ | 1828376966645940224 |
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| author | Manuela Gaebler Alessandra Silvestri Johannes Haybaeck Johannes Haybaeck Peter Reichardt Caitlin D. Lowery Louis F. Stancato Gabriele Zybarth Christian R. A. Regenbrecht |
| author_facet | Manuela Gaebler Alessandra Silvestri Johannes Haybaeck Johannes Haybaeck Peter Reichardt Caitlin D. Lowery Louis F. Stancato Gabriele Zybarth Christian R. A. Regenbrecht |
| author_sort | Manuela Gaebler |
| collection | DOAJ |
| description | Over the past decade, the development of new targeted therapeutics directed against specific molecular pathways involved in tumor cell proliferation and survival has allowed an essential improvement in carcinoma treatment. Unfortunately, the scenario is different for sarcomas, a group of malignant neoplasms originating from mesenchymal cells, for which the main therapeutic approach still consists in the combination of surgery, chemotherapy, and radiation therapy. The lack of innovative approaches in sarcoma treatment stems from the high degree of heterogeneity of this tumor type, with more that 70 different histopathological subtypes, and the limited knowledge of the molecular drivers of tumor development and progression. Currently, molecular therapies are available mainly for the treatment of gastrointestinal stromal tumor, a soft-tissue malignancy characterized by an activating mutation of the tyrosine kinase KIT. Since the first application of this approach, a strong effort has been made to understand sarcoma molecular alterations that can be potential targets for therapy. The low incidence combined with the high level of histopathological heterogeneity makes the development of clinical trials for sarcomas very challenging. For this reason, preclinical studies are needed to better understand tumor biology with the aim to develop new targeted therapeutics. Currently, these studies are mainly based on in vitro testing, since cell lines, and in particular patient-derived models, represent a reliable and easy to handle tool for investigation. In the present review, we summarize the most important models currently available in the field, focusing in particular on the three-dimensional spheroid/organoid model. This innovative approach for studying tumor biology better represents tissue architecture and cell–cell as well as cell–microenvironment crosstalk, which are fundamental steps for tumor cell proliferation and survival. |
| first_indexed | 2024-04-14T08:07:51Z |
| format | Article |
| id | doaj.art-37282d9a1fa941e082fd6a76176c1389 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-14T08:07:51Z |
| publishDate | 2017-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-37282d9a1fa941e082fd6a76176c13892022-12-22T02:04:41ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2017-09-01710.3389/fonc.2017.00203287187Three-Dimensional Patient-Derived In Vitro Sarcoma Models: Promising Tools for Improving Clinical Tumor ManagementManuela Gaebler0Alessandra Silvestri1Johannes Haybaeck2Johannes Haybaeck3Peter Reichardt4Caitlin D. Lowery5Louis F. Stancato6Gabriele Zybarth7Christian R. A. Regenbrecht8HELIOS Klinikum Berlin-Buch GmbH, Department of Interdisciplinary Oncology, Berlin, Germanycpo – Cellular Phenomics & Oncology Berlin-Buch GmbH, Berlin, GermanyMedical Faculty, Department of Pathology, Otto-von-Guericke University Magdeburg, Magdeburg, GermanyInstitute of Pathology, Medical University Graz, Graz, AustriaHELIOS Klinikum Berlin-Buch GmbH, Department of Interdisciplinary Oncology, Berlin, GermanyEli Lilly and Company, Oncology Translational Research, Lilly Corporate Center, Indianapolis, IN, United StatesEli Lilly and Company, Oncology Translational Research, Lilly Corporate Center, Indianapolis, IN, United Statescpo – Cellular Phenomics & Oncology Berlin-Buch GmbH, Berlin, Germanycpo – Cellular Phenomics & Oncology Berlin-Buch GmbH, Berlin, GermanyOver the past decade, the development of new targeted therapeutics directed against specific molecular pathways involved in tumor cell proliferation and survival has allowed an essential improvement in carcinoma treatment. Unfortunately, the scenario is different for sarcomas, a group of malignant neoplasms originating from mesenchymal cells, for which the main therapeutic approach still consists in the combination of surgery, chemotherapy, and radiation therapy. The lack of innovative approaches in sarcoma treatment stems from the high degree of heterogeneity of this tumor type, with more that 70 different histopathological subtypes, and the limited knowledge of the molecular drivers of tumor development and progression. Currently, molecular therapies are available mainly for the treatment of gastrointestinal stromal tumor, a soft-tissue malignancy characterized by an activating mutation of the tyrosine kinase KIT. Since the first application of this approach, a strong effort has been made to understand sarcoma molecular alterations that can be potential targets for therapy. The low incidence combined with the high level of histopathological heterogeneity makes the development of clinical trials for sarcomas very challenging. For this reason, preclinical studies are needed to better understand tumor biology with the aim to develop new targeted therapeutics. Currently, these studies are mainly based on in vitro testing, since cell lines, and in particular patient-derived models, represent a reliable and easy to handle tool for investigation. In the present review, we summarize the most important models currently available in the field, focusing in particular on the three-dimensional spheroid/organoid model. This innovative approach for studying tumor biology better represents tissue architecture and cell–cell as well as cell–microenvironment crosstalk, which are fundamental steps for tumor cell proliferation and survival.http://journal.frontiersin.org/article/10.3389/fonc.2017.00203/fullsarcomapreclinical modelin vitro organoid culturepatient-derived in vitro modeldrug screeningsarcoma treatment |
| spellingShingle | Manuela Gaebler Alessandra Silvestri Johannes Haybaeck Johannes Haybaeck Peter Reichardt Caitlin D. Lowery Louis F. Stancato Gabriele Zybarth Christian R. A. Regenbrecht Three-Dimensional Patient-Derived In Vitro Sarcoma Models: Promising Tools for Improving Clinical Tumor Management Frontiers in Oncology sarcoma preclinical model in vitro organoid culture patient-derived in vitro model drug screening sarcoma treatment |
| title | Three-Dimensional Patient-Derived In Vitro Sarcoma Models: Promising Tools for Improving Clinical Tumor Management |
| title_full | Three-Dimensional Patient-Derived In Vitro Sarcoma Models: Promising Tools for Improving Clinical Tumor Management |
| title_fullStr | Three-Dimensional Patient-Derived In Vitro Sarcoma Models: Promising Tools for Improving Clinical Tumor Management |
| title_full_unstemmed | Three-Dimensional Patient-Derived In Vitro Sarcoma Models: Promising Tools for Improving Clinical Tumor Management |
| title_short | Three-Dimensional Patient-Derived In Vitro Sarcoma Models: Promising Tools for Improving Clinical Tumor Management |
| title_sort | three dimensional patient derived in vitro sarcoma models promising tools for improving clinical tumor management |
| topic | sarcoma preclinical model in vitro organoid culture patient-derived in vitro model drug screening sarcoma treatment |
| url | http://journal.frontiersin.org/article/10.3389/fonc.2017.00203/full |
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